Apixaban, i.e., 1-(4-methoxylphenyl)-7-oxo-6-[4-(2-oxo-1-piperidyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridyl-3-carboxamide, has the following structural formula:

Apixaban is an oral anticoagulant jointly developed by Pfizer and Squibb, acting as an inhibitor of Xa factor. Apixaban is now marketed in China, US and Europe. In China, it is approved for adult patients undergoing elective hip-joint or knee-joint replacement, and for preventing venous thrombus embolism (VTE). Its marketing provides a safe and effective new choice for anticoagulation after clinical orthopedic surgery, bringing out good news for the patients of elective hip-joint or knee-joint replacement in China. Clinical trials show that Apixaban has better effect than enoxaparin.
Each of 1-(4-nitrophenyl)piperidyl-2-one and 5,6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo-1-piperidyl)phenyl]-2(1H)-pyridone compounds is one of the key intermediates for synthesizing Apixaban, the relevant preparing methods of which are currently reported as follow:                1. CN publication No. CN101065379 discloses a method for preparing 1-(4-nitrophenyl)piperidyl-2-one comprising reacting paranitroaniline with 5-bromo-valeryl chloride in base through amidation and cyclization two steps reaction. The reaction scheme is as follow:        
                2. CN publication No. CN101967145 discloses a preparing method having the reaction scheme of:        

The primary problems suffered by these methods lie in that:
1) The quality control and preparation process is relatively difficult and the cost is relatively high because of using 5-bromo-valeryl chloride as raw material. Using organic base such as potassium tert-butoxide and the like as the base, and tetrahydrofuran as the solvent leads to the high cost, and thus they are not suitable for industrial production.2) In the above reactions, the amidation reaction is carried out by a tertiary amine organic base of triethylamine and the cyclization reaction is carried out by a stronger base of sodium tert-butoxide, potassium tert-butoxide, or sodium hydride. These methods use very hazardous sodium hydride and have the disadvantages of complicated operations, tedious post-treatment and being relatively difficult quality control of product.